| Popis: |
Polnjenje več vrst pelet v eno kapsulo nam omogoča aplikacijo več zdravilnih učinkovin z enim farmacevtskim izdelkom ali kombiniranje kinetike sproščanja iste zdravilne učinkovine. To omogoča lažjo uporabo zdravil in večjo soglasnost pacienta. Kombinacija pelet z zdravilno učinkovino in nevtralnih peletnih jeder v zmesi olajša izdelavo kapsul z različnimi odmerki. Namen naloge je bil oceniti obseg segregacije dvokomponentnih zmesi pelet pri industrijskem procesu kapsuliranja ter določiti kritično razliko v velikosti pelet, kjer segregacijo lahko pričakujemo. Poleg vpliva razlik v velikosti smo proučevali še vpliva površine pelet in načina polnjenja zalogovnika kapsulirke. Štiri različne vrste pelet (obarvane pelete s tartrazinom, aktivne pelete z učinkovino in dve vrsti nevtralnih peletnih jeder (različnih po velikosti)) smo kombinirali v štirih binarnih zmeseh, ki smo jih v pilotnem procesu kapsuliranja polnili v kapsule, pri tem pa smo predhodno spreminjali še način polnjenja zmesi v zalogovnik kapsulirke. Določili in potrdili smo kritične točke procesa in dejavnike, ki na pojav segregacije pri tem procesu vplivajo. Trdne želatinaste kapsule smo vzorčili v posameznih časovnih fazah kapsuliranja in jih po skupinah analizirali glede na fizikalne oziroma farmacevtsko-tehnološke lastnosti pelet. Za namen analize odvzetih vzorcev smo razvili metodo, s katero smo vzorec optično zajeli in iz parametrov izračunali deleže posameznih komponent v kapsulah. Razvito metodo smo tudi validirali. Iz parametrov velikosti oziroma barve posameznih komponent smo izračunali volumske deleže posameznih komponent v kapsuli in jih med seboj primerjali skozi celoten čas kapsuliranja, kar nam je dalo vpogled v spremembe razmerij posameznih komponent zmesi tekom procesa. Na podlagi dobljenih rezultatov lahko trdimo, da je moč globalno segregacijo peletne zmesi in lokalno homogenost zmesi zagotoviti le, če se delci posameznih komponent kapsule ne razlikujejo v velikosti in hkrati izkazujejo podobne površinske lastnosti. Kot kritične točke kapsuliranja smo opredelili začetek in konec kapsuliranja, kjer se najbolj izrazijo vplivi procesov perkolacije in rešetanja pri sipanju zaradi razlik v velikosti ter predvidoma tudi v površini pelet. V teh točkah procesa je največja verjetnost, da bomo zaznali segregacijo zmesi. Dejavnik, ki prav tako vpliva na celoten proces kapsuliranja in izraženost segregacije, kot tudi lokalne nehomogenosti zmesi, je predhodno mešanje različnih vrst pelet. S tem raziskovalnim delom smo potrdili, da ima na segregacijo zmesi vpliv veliko dejavnikov in da moramo večkomponentne kapsule načrtovati in izdelati s premislekom. Za preučevane zmesi predvidevamo, da je bila razlika v velikosti delcev glavni razlog za segregacijo. Filling several types of pellets into one capsule allows us to administer multiple active ingredients with one pharmaceutical product or to combine different release kinetics of one active ingredient. The combination of pellets with active ingredient and neutral pellet cores in the mixture facilitates the production of capsules with different strengths. The purpose of the study was to evaluate the extent of segregation of two-component pellet mixtures within the industrial encapsulation process and to determine the critical difference in pellet size, where segregation can be expected. In addition to the effect of size differences, the effect of the pellet surface and the method of filling the capsule filling machine bin was also studied. Four different types of pellets (coloured pellets with tartrazine, pellets with active substance and two types of neutral pellet cores (different in size)) were combined into four binary mixtures, which were then filled into capsules in a pilot encapsulation process, which was preceded by different bin pellet filling method. Solid gelatine capsules were sampled at individual time stages of encapsulation and analysed by groups according to the physical properties of the pellets. For the purpose of analysing the samples taken, a method was developed, by which the sample was optically captured and the mass proportions of the individual components in the capsules were calculated from the parameters. The method was validated. From the size parameters or colour of the individual components, the volume fraction of each component in the capsule was calculated and compared over the entire encapsulation time, which gave us insight into changes in the proportions of the individual components of the mixture during the process. Based on the results obtained, it can be argued that the global segregation of the pellet mixture and the local homogeneity of the mixture can only be ensured if the particles of the individual components of the capsule do not differ in size and exhibit similar surface properties. The critical point of encapsulation is defined as the start and the end of capsulation process, where the effects of percolation and sifting, due to differences in particle size and surface properties, are most pronounced. At these points, the mixture is most likely to segregate. A factor that also affects the entire capsule filling and segregation process is the mixing of different types of pellets. With this research work, we have confirmed that many factors influence the segregation of a pellet mixture and that multicomponent capsules must be designed and manufactured with consideration. For studied mixtures, we assume that the particle size difference was the main reason for segregation. |
